The Study to Help the AIDS Research Effort (SHARE) along with three other clinical sites (Northwestern University, Chicago, Illinois; UCLA School of Public Health, Los Angeles, California; Pittsburgh-Graduate School of Public Health, Pittsburgh, Pennsylvania) collectively know as MACS was funded by National Institute of Allergy and Infectious Disease (NIAID) in 1983 and began recruiting AIDS-free homosexual and bisexual men in 1984 for a natural history study of AIDS, subsequently redefined as the natural history of HIV-1 infection. The original goals of the MACS were to define risk factors for acquisition of HIV-1 infection, mechanisms of AIDS pathogenesis and specific incidences and risk factors for particular clinical manifestations of HIV-1 infection, such as infections, malignancies and neuropsychological impairments. Funding for the SHARE study was renewed for four years in April 1999. The study consists of several components working together to achieve the following specific aims: -To determine the long-term effectiveness, at the population level, of highly active antiretroviral therapy (HAART) -To delineate the determinants of individual response to therapy -To further characterize host genetic factors, immune responses and virologic characteristics specific to participants who demonstrate progression of HIV-1 infection, in contrast to those who are on progressors, with particular emphasis on characteristics pertinent to development of vaccines and therapy -To further characterize the nature of host-mediated resistance in highly exposed HIV-1 uninfected participant -To continue efforts to refine and extend prognostic markers of disease progression -To determine factors that contribute to specific disease outcomes -To determine the epidemiology and pathogenesis of HIV-1 malignancies Cohort maintenance is paramount to achieving the specific aims. Ninety-five percent of participant visits take place in the GCRC during regular clinic hours on Tuesday and Friday evenings. There are a small percentage of men who, for a number of reasons (illness, schedule conflict) are not able to attend clinic. Study staff continue to create ways to meet the needs of the study and the participants. Utilizing regular clinic hours, non-clinic hours and off-site facilites, we have been able to maintain a follow-up rate of 75% among the seropositive cohort.